Hello guys I've been searching for almost 2 yrs on the subject, and searched almost all the studies, and here's how accutane is definitly accelerating our genetic baldness with 4 factors:
An exogenous apport of retinoic acid in the metabolism (like we had for treating acne) make long term changes in the level of all trans retinoic acid (atRA) produced in each of our cells ( sebaceous glands cells, IF cells and dermal papilla cells). Aldh1a3 is the gene who is responsible of transforming the enzymes into atRA, his activity/expression determine the level of atRA in dermal papilla cells. Aldh1a1 determine the level of atRA in SB cells and aldh1a2 in bulge region cells.
Our treatment with high isotretinoin administration make a long term change on those genes epressions, so that those genes are now more active and so the level of atRA in each of our follicle cells are constantly higher than it should.
Now let's look what high atRA level in each of our cells is doing, and how it can accelerate our baldness:
1) atRA upregulate the rate transformation of DHT into 5alpha-DHT !
"Administration of all-trans-retinoic acid to male rats increased the rate of 5alpha-dihydrotestosterone (5alpha-DHT) formation from testosterone in microsomal fractions in vitro."
http://www.ncbi.nlm.nih.gov/pubmed/10423178
2) The more atRA, the less WNT activity ! RA signaling and WNT pathway work together, they regulate each other for many things .
"We identified a signaling cascade through which retinoic acid switches off Wnt"
"these results further indicate that RA inhibits WNT signaling"
"Our 3 preliminary studies indicate that RA does indeed interact with WNT signaling in the hair"
""Follicular localization sites (including hair follicle stem cells) of several WNT signaling molecules are similar to those of synthesis enzymes of retinoic acid (RA), a vitamin A metabolite."
"All trans-Retinoic Acid Mediates Wnt/β-catenin Signaling through MED28 in Human Colon Cancer Cells"
"All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation"
Well I stop here (you can write the sentences in Google to find each study), they are hundreds of other studies explaining the interaction between RA activity and WNT and so in each of our follicle cells (more importantly DP cells), there's too high atRA level, so automatically less activation of WNT.
3) the more atRA, the less PPAR protection (alteration of vitaminA metabolism lead to hair loss)
PPARy deletion is critical in cicatricial alopecias ( FFA, PCA, CCCA, LPP,..)
http://dermatologytimes.modernmedic...amma-cicatricial-alopecia-under-inv?page=full
http://www.jidonline.org/article/S0022-202X(15)34340-2/abstract
And now they showed how altered retinoid metabolism (what we did with accutane) is involved in alopecias like CCCA and CA:
-At the 2015 North American Hair Research Society Scientific Meeting, there this presentation : "Alterations of vitamin A metabolism and signaling in central, centrifugal, cicatricial alopecia patients"
-or this study : "Retinoid metabolism is altered in human and mouse cicatricial alopecia"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546159/
-In this other recent study they explain how altered metabolism VItaminA regulation is connected to CCCAlopecia, and how excess of RA synthesis silenced the WNT signaling https://etd.ohiolink.edu/ap/10?0::NO...D_SUBID:103145
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Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis, whereas excess RA is well known as a teratogen. In humans, excess RA is associated with hair loss.
"Our results show that normalization of RA levels is associated with reinitiation of hf development."
http://www.jbc.org/content/287/47/39304.full
CCCA hair loss is diffuse long term hair loss beginning generally on vertex , BUT that work together in synergy with genetic baldness so the whole thing follow a classic baldness pattern (studies reporting the difficulty of diagnosting CCCA in patients because of that). So yes our genetic balness could also be accelerated by cicatricial alopecia factors (less wnt, less anti inflammation protection,etc ) because of our altered vitamin A metabolism that lead to too high atRA level in every of our follicle cells
4) the more atRA , the less insulin-like growth factor-1 (IGF-1) !
"Short-term isotretinoin treatment decreases insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels"
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2009.09618.x/abstract And atRA also impact the NOTCH1 and TGFβ pathway !
http://www.jbc.org/content/early/2015/05/27/jbc.M115.638510
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so it's easy understable that if we have now higher atRA levels in each of our cells, we combine these 4 negative factors in each of them. And all met together in each different HF cells for infine the destruction of the follicle: in each of our dermal papilla cells for ex there's a higher rate of DHT to 5ARdht transformation, a silenced WNT pathway, no more anti inflammation protection, and less HF growth factors, all because of higher atRA than normal, so the combination definitly aggravate or even trigger our hair loss.
Don't forget that each individual metabolism don't react the same with exogenous RA administration. So for some people, the treatment will lead to dramatic changes in skin cells genes expression, and so high changes for life in cells atRA levels. For others the changes will be less strong, but still the atRA levels will be higher than it should. And for others the treatment won't be sufficient to impact the genes expression for long term;
Everyone's metabolism react differently, but whatever the scale, if accutane worked for your acne, that mean cells genes expressions changes and so higher atRA levels for long term, and so it's linked with the speed of our hair loss development
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THERE IS A SOLUTION
we are surely combining those 4 negative factors because of our higher atRAs levels (each individual in a different proportion of course), and so we need to eradicate these 4 aggravating factors by lowering the atRA levels.
What is determining the level of atRA in dermal papilla cells is the activity of Aldh1a3 (his role is to transform the enzymes into atRA, the more he is active, the higher level of atRA)
So I search about this, and what I found first is that inhibition of aldh1a3 is possible via the inhibition of the STAT3 pathway !! What a great surprise it was!
"Inhibition of STAT3-NFkB activity allowed high levels of DDIT3 expression with increased formation of a DDIT3-CEBPβ complex.
This reduced the occupancy of the ALDH1A3 promoter by CEBPβ, thus largely reducing the ALDH1A3 expression."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494963/
I'm sure you all aware of the jak/stat3 inhibitors recently tested for alopecias areata and universalis. So it was good surprise when i searched about aldh1a3 inhibition and found the connexion with jak/stat3 pathway.
all of this show that it can work for us to at least suppress the 4 aggravating factors by inhibiting aldh1a3 and so the atRA levels in our dermal papillas cells = less 5ARdht formation + more WNT + more PPAR protection + more IGF-1 and IGFBP3 + less negative interactions with TGF and notch pathway
So yes we definitly have to correct what accutane changed in our follicles cells if we want to fight our balness progress.
Everyone of us who have higher atRAs than the normal will benefit of it as we'll become free of the 4 aggravating factors that kill the follicles. So some of us could expect dramatic positive results I think.
So now I search in France a Professional/clinic/dermato/etc, I will send them the whole facts explication with all the studies, and they should easily understand why testing a topical jak/stat could benefit my 'genetic baldness aggravated by acutane alteration of vitaminA metabolism'.
If i don't find in France, i will already begin the natural way and search for a comprehensive doctor/clinic in other countries.
So If you are in the same case as me and want to try, I encourage you to talk at some professionnals about it, ask them what they think about this, show the studies, and they will logically understand why you want to give it a try like in the other alopecias cases (AA and AU). they'll for sure understand why we want to suppress the things that accelerate/aggravate/maybe even trigger our baldness in our alopecia case. It's sure we can find some Professionals that could be interested to see what it does in cases like us.
I begin in France but will also search in other countries, I need the 6 month treatment test to see what it does! With all these studies I can't wait for more years, cause all suggest it'll definitly be benificial for my hair loss, but what I really want and can't wait to know is in which proportion! I fckn need that answer^^
So tell me if you see some error or contradictions above, but everything I wrote comes from the studies of well known scientists specialized in dermatology, and infine everything fits
accutane can induce longterm high atRAs level expression in the cells =high atRA induce 4 factors that induce hair loss = with this hell of a combination, we develop our predisposed balness faster (maybe even really faster) than what it should have been normally. And those factors explain also why some of us also have hard thinning of the donor area at such a young age
